Is CDH10 p.Arg128Cys (c.382C>T) pathogenic?

CDH10 p.Arg128Cys (c.382C>T) is classified Uncertain significance in CDH10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.6408); Very rare (popmax 0.00935%, afr).

How common is CDH10 p.Arg128Cys (c.382C>T) in the general population?

CDH10 p.Arg128Cys (c.382C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about CDH10 p.Arg128Cys (c.382C>T)?

AlphaMissense predicts likely pathogenic (score 0.6408) — an in-silico prediction, not a clinical call.

CDH10 p.Arg128Cys

c.382C>T · VCV4831710

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6408 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6408	likely pathogenic
REVEL	0.365	indeterminate
SaProt	LLR -10.19	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 46 kb · p 1.8e-06 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,836 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.0026% 42/1,613,094 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,691
European (non-Finnish)	0.00271%	36,859
East Asian	0.00223%	44,838
Remaining individualsnot grpmax-eligible	0.0016%	62,434
South Asian	0.0011%	91,060

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDH10
Protein: p.Arg128Cys
Coding: c.382C>T
MANE Select: NM_006727
Type: single nucleotide variant
Location: chr5:24537524 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 78.29
Residue 128: the cadherin 1 domain

Full CDH10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH10 p.Met316Ile Uncertain significance ★★ ⚠ same type
CDH10 p.Thr159Met Uncertain significance ★★ ⚠ same type
CDH10 p.Glu469= Benign ★★ same type
CDH10 p.Gly673= Benign ★★ same type
CDH10 p.Ala296Thr Uncertain significance ★ ⚠ same type
CDH10 p.Ala501Val Uncertain significance ★ ⚠ same type
CDH10 p.Ala530Val Uncertain significance ★ ⚠ same type
CDH10 p.Arg268Cys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cdh10-p-arg128cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown